Venting system

ABSTRACT

Biological fluid processing assemblies having a gas inlet and/or a gas outlet are disclosed.

This disclosure is a continuation of patent application Ser. No.08/451,490, filed May 26, 1995, abandoned which is filed Nov. 18, 1992,which is the U.S. National phase of PCT application no. PCT/US91/03616,filed May 24, 1991, now U.S. Pat. No. 5,451,321, which is acontinuation-in-part of Ser. No. 07/528,160, filed May 24, 1990 now U.S.Pat. No. 5,126,054.

TECHNICAL FIELD

The present invention relates to a system for processing donated bloodinto its therapeutically valuable blood components and derivativetherapy, and more particularly to improved methods and means for ventingair and other gases entrapped in a blood processing system, and toimproved methods and means for the recovery of substantially all of theblood products derived from the donated blood.

BACKGROUND OF THE INVENTION

The development of plastic blood collection bags has facilitated theseparation of donated whole blood into its various components andanalogous products, including factors, concentrates, and therapeuticserum, thereby making these different blood products available as atransfusion product. The separation of a single unit of donated wholeblood, about 450 milliliters in USA practice, into its components istypically accomplished by use of differential sedimentation usingcentrifugation, as is well known to those skilled in the art.

A typical procedure used in the United States, thecitrate-phosphate-dextrose-adenine (CPDA-1) system, utilizes a series ofsteps to separate donated blood into three components, each componenthaving substantial therapeutic and monetary value. The proceduretypically utilizes a blood collection bag which is integrally attachedvia flexible tubing to at least one, and preferably two or more,satellite bags. Using centrifugation, whole blood may be separated bydifferential sedimentation into such valuable blood components asplasma, packed red cells (PRC), platelet-rich plasma (PRP), plateletconcentrate (PC), and cryoprecipitate (which may require extraprocessing in order to obtain). The plasma may itself be transfused intoa patient, or it may be separated by complex processes into a variety ofother valuable blood products.

With the passage of time and the accumulation of research and clinicaldata, transfusion practices have changed greatly. One aspect of currentpractice is that whole blood is rarely administered; rather, patientsneeding red blood cells are given packed red cells, patients needingplatelets are given platelet concentrate, and patients needing plasmaare given plasma.

For this reason, the separation of blood into components has substantialtherapeutic and monetary value. This is nowhere more evident than intreating the increased damage to a patient's immune system caused by thehigher doses and stronger drugs now used during chemotherapy for cancerpatients. These more aggressive chemotherapy protocols are directlyimplicated in the reduction of the platelet content of the blood toabnormally low levels; associated internal and external bleedingadditionally requires more frequent transfusions of PC, and this hascaused platelets to be in short supply and has put pressure on bloodbanks to increase platelet yield per unit of blood.

One of the problems attendant with the separation of various bloodcomponents using a multiple bag system and centrifugation is that highlyvaluable blood component become trapped in the conduits connecting thevarious bags and in the various biomedical devices that may be used inthe system. It is an object of this invention to provide apparatuses andmethods which permit the recovery of these valuable blood components.

In blood processing systems, air, in particular oxygen, present instored blood and blood components, or in the storage container, may leadto an impairment of the quality of the blood components and may decreasetheir storage life. More particularly, oxygen may be associated with anincreased metabolic rate (during glycolysis), which may lead todecreased storage life, and decreased viability and function of wholeblood cells. For example, during storage red blood cells metabolizeglucose, producing lactic and pyruvic acids. These acids decrease the pHof the medium, which in turn decreases metabolic functions. Furthermore,the presence of air/gas in the satellite bag may present a risk factorto a patient's being transfused with a blood component. For example, aslittle as 5 ml may cause severe injury or death. Despite the deleteriouseffect of oxygen on storage life and the quality of blood and bloodcomponents, the prior art has not addressed the removal of gases fromblood processing systems during the initial collection and processingsteps. It is, therefore, an object of this invention to provide asterile blood processing system in which gases present in the system areseparated from the blood or blood product.

Another problem has been maintaining the sterility of the processingsystem. The word sterility, as used herein, refers to maintaining asystem free from viable contaminating microorganisms. Exemplary methodsof determining sterility include tests using fluid thioglycollate mediumor using soybean-casein digest medium, described in more detail in theU.S. Code of Federal Regulations (21 CFR 610.12).

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention, there isprovided a blood processing system which includes means for removing asfrom the various components of the system in order to improve thestorage life, safety, and high quality of the processed blood.

In accordance with another aspect of this invention, a blood processingsystem is provided wherein liquid trapped in various elements of theblood processing system is recovered either by causing a volume of gasbehind the entrapped liquid to push the liquid through those elementsand into the designated collection bag, or by pulling the entrappedliquid into the designated collection bag by a pressure differential(e.g., gravity head, pressure cuff, suction, and the like).

In accordance with yet another aspect of the invention, it will beappreciated that a means of the present invention is useful in anyliquid transfer or delivery system where there is to be a one timeremoval of gases from the system and the ingress of gases into thesystem during liquid transfer or delivery is to be prevented, including,for example, such systems that are to be primed for future liquidtransfer or systems that are to be filled to a predetermined level.

The gas inlet and gas outlet of the present invention is particularlywell adapted for use in pharmaceutical and medicinal applications, andin medical and pharmaceutical devices; and embodiment of the inventionis particularly suited for use in devices where gases present in suchsystems must be vented or where gases must be prevented from reaching apatient receiving an injection of the liquid.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an embodiment of a blood processing system which includes agas inlet and a gas outlet in the conduits in sealed communication withthe bags, according to the invention.

FIG. 2 is another embodiment of a blood processing system according tothe invention, illustrating a blood collection system for separatingwhole blood into packed red cells, platelet concentrate, and plasma.

FIGS. 3A and 3B are embodiments of a blood processing system accordingto the invention which include gas inlet and gas outlet in sealedcommunication with separate gas storage means. FIG. 3A multiple gasstorage means and 3B, a single gas storage means.

FIG. 4 is an embodiment of a blood processing system according to theinvention, in which the gas from the system is recycled and stored forreuse.

FIG. 5 is a modified assembly including connector means on each end of aconduit having a gas inlet, a functional biomedical device, and a gasoutlet.

FIGS. 6A, 6B, and 6C are exemplary configurations of gas inlet and gasoutlet according to the invention.

FIG. 7 is a vertical sectional view of an embodiment of a gas outletaccording to the invention.

FIG. 8 is a perspective view of an intravenous feeding system, includinga gas outlet for the passage of gas from the administration set.

FIGS. 9A and 9B are an administration assemblies including a functionalbiomedical device and a gas outlet.

FIG. 10 is a collection bag communicating with a gas inlet.

FIG. 11 is an embodiment of a blood processing system including a gasinlet and a functional biomedical device having an additional gas inlet.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention primarily involves a sterile blood processingsystem for the post-donation processing of donated blood into valuableblood products. However, it is intended that the invention is not to belimited by the type of fluid being processed or administered. Anybiological fluid, such as a saline solution, a medicant solution, or anutrient solution, which are processed or administered using devices orassemblies which contain or collection air or gas, are included withinthe scope of the present invention. Below, the invention will bedescribed using blood or a blood product as the biological fluid, but itshould be evident that other biological fluids may be incorporated intothe blood processing or administration systems described herein.

In the present invention, means and methods are provided to remove air,oxygen, and other gases from a system in order to minimize the volume ofgases that remain in, or in contact with, a blood product duringstorage. Means and methods are also provided for the recovery ofvaluable blood and blood products that may become entrapped in thevarious elements of the system during blood processing and which wouldotherwise be lost.

The gas outlet may be any of a variety of means and devices which arecapable of separating gas such as air, oxygen and the like, that may bepresent in a blood processing system from the liquid, i.e., blood and/orblood components that are processed in the system. The gas inlet may beany of a variety of means and devices which are capable of allowing gas,such as air, oxygen, and the like, into a processing system. As usedherein, gas refers to any gaseous fluid, such as air, sterilized air,oxygen, carbon dioxide, and the like; it is intended that the inventionis not to be limited thereby.

Additionally, the gas inlet and gas outlet are chosen so that thesterility of the system is not compromised. The gas inlet and the gasoutlet are particularly suited for use in closed systems, or withinabout 24 hours of a system being opened. Suitable gas inlet and gasoutlet include a liquophobic porous medium with a sufficiently smallpore size to preclude the ingress of bacteria into the system. Becausethe liquophobic porous medium is not wettable by the blood and bloodproduct being processed in the system, gas in the system that contactsthe liquophobic medium will pass through it and the blood or bloodproducts will not be absorbed by the liquophobic porous medium.Typically, the pore size of the liquophobic porous medium will be lessthan 0.2 microns to provide a satisfactory bacterial barrier.

Typical blood processing assemblies include at least two containersconnected by a conduit (see for example, FIGS. 1 and 3). While at leastone gas inlet or gas outlet may be interposed between such a simple twobag system, it is more likely that the venting means in according withthe invention will be more useful in more complicated processing system,having for example, one or more functional biomedical devices, such as aseparatory or filter device, interposed between the containers (see forexample, FIGS. 2 and 4).

In its simplest aspect, the present invention involves a bloodprocessing assembly comprising a conduit, a gas inlet and/or a gasoutlet in the conduit, and a functional biomedical device. See, forexample, FIG. 5. This embodiment of the invention may have a needle orthe like attached to one end of the conduit so that the assembly may beused, for example, as an intravenous feeding device. This embodiment mayalso be configured, as illustrated in FIGS. 5 and 9, with a connectormeans on an end or ends of the assembly.

In other, more complex aspects, the present invention may involve ablood processing assembly comprising a first container and a secondcontainer, and a conduit interconnecting the first container with thesecond container; and, optionally, at least one third container and aconduit interconnecting the first container with the third container;and having interposed between the first container and a secondcontainer, at least one functional biomedical device; and havinginterposed between the first container and the second container, atleast one gas inlet or gas outlet.

With the increased acceptance of transfusion therapy in the treatment ofa number of disorders and conditions, physicians have found it necessaryor desirable to transfuse multiple blood units, each of which istypically leucocyte-depleted during administration. Whether theadministration set comprises multiple bags and a single high capacityleucocyte filter, or multiple bags and multiple filters, gas in theadministration assembly may present a substantial risk. Thus, inaccordance with another embodiment of the invention, a typicaladministration assembly includes a first conduit having a spike or thelike on one end and a functional biomedical device, such as a leucocytedepletion filter, on the other end. A second conduit leads from thebiomedical device and typically has a connector on the downstream end.In accordance with the present invention, a gas outlet is disposed inthe second conduit downstream of the biomedical device; and a gas inletmay be disposed in the first conduit between the spike and thebiomedical device. It is further preferred that the assembly includes apre-primed functional biomedical device.

Pre-priming, as used herein, refers to wetting or priming the innersurfaces of an assembly prior to its actual use. For example, using thedevice illustrated in FIG. 9a, the spike may be inserted into a solutioncontainer; the clamp is opened to allow fluid to flow through theassembly; then, with the passage of fluid through the assembly, gasdownstream of the fluid is expelled through the gas outlet until fluidreaches the branching element, at which point the clamp is closed. Withthe clamp in a closed position, the connector downstream of the gasoutlet may be opened or readied for use without fluid in the assemblydripping through the connector.

According to another embodiment of the invention, a gas inlet or a gasoutlet may be disposed in a conduit having a connector on both ends. Inthis way, the embodiment may be inserted into a previously existingsystem. For example, if one of the connectors is a spike, the spike canbe inserted into a container; in this way a fluid flow path may beestablished which is capable of utilizing a gas inlet or a gas outlet inany of the ways described in accordance with this invention. Oneembodiment of such an assembly is illustrated in FIG. 5, in which spike50 and connector 51 may be used to attach the assembly to a pre-existingfluid processing or administration set. In another embodiment,illustrated in FIG. 9b, a component may be easily and aseptically addedto a pre-existing fluid processing or administration set: a spikeconnector leading from a medication container or the like may beinserted into a previously existing assembly by inserting the spikethrough a gas inlet or gas outlet of the invention. In this embodiment,the spike penetrates the membrane, establishing an aseptic connection.

Blood, as used herein, refers to the following: whole blood;anti-coagulated whole blood (AWB); packed red cells (PRC) obtained fromAWB; platelet-rich plasma (PRP) obtained from AWB; platelet concentrate(PC) obtained from AWB or PRP; plasma obtained from AWB or PRP; redcells separated from plasma and resuspended in physiological fluid;cryoprecipitate; platelets separated from plasma and resuspended inphysiological fluid; and any of the above mixed with or suspended in aphysiological fluid. As used herein, blood refers to the componentsdescribed above, and to similar or analogous blood products obtainedfrom any of the above, or by other means, or with similar properties. Inaccordance with the invention, each of these blood products may beprocessed in the manner described herein.

A functional biomedical device, as used herein, may be any of a numberof devices or assemblies in which air or gases are present and/or maycollect or form, or should be displaced prior to use of the assembly.Exemplary functional biomedical devices include a filter, such as aleucocyte depletion filter; a separatory device, such as a plateletconcentrator, preferably a non-centrifugal platelet concentrator; adebubbler; a pump; and a connector. The functional biomedical device mayalso include a device for destroying biological contaminants, such as ahigh intensity light wave chamber, or a device for sampling a biologicalliquid.

In accordance with the invention, a clamp, closure, or the like may bepositioned on or in any or all of the conduits in order to facilitate adesired function, i.e., establishing a desired flow path for bloodproduct or gas. For example, when processing a blood product through asystem such as is illustrated in FIG. 3B, during the removal of gasesfrom conduit 12, functional biomedical device 14 and conduit 15, it maybe desirable to clamp conduit 15 immediately below gas outlet 16 and toclamp conduit 37 immediately above gas storage means 35. When it isdesirable to use the gas in gas storage means 35 to maximize therecovery of blood product, the clamp below gas outlet 16 is released, aclamp adjacent to gas storage means 35 in conduit 36 is closed, a clampin conduit 37 adjacent to gas storage means 35 is opened, and a clamp inconduit 37 adjacent to gas intake means 13 is opened.

In accordance with the invention, the processing system is provided witha gas inlet to permit the introduction of air or gas into the systemafter most of the processing has taken place, and/or with a gas outletto permit gases in the various elements of the system to be separatedfrom the liquid to be processed. It is intended that gas inlet and thegas outlet may both be used in a blood processing system, or therespective gas inlet or gas outlet may be used alone.

To that end, a gas inlet or gas outlet may be included in any of thevarious elements of the assembly. By way of illustration, gas inlet orgas outlet may be included in at least one of the conduits which connectthe different containers, in a wall of the containers that receive theprocessed blood and/or blood product, or in a port on or in one of thosecontainers. The gas inlet or gas outlet may also be included on or in acombination of the elements mentioned above. Also, a functionalbiomedical device may include one or more gas inlets or gas outlets. Forexample, in the embodiment illustrated in FIG. 11, the functionalbiomedical device 14 includes a gas inlet 13A. Generally, however, it ispreferred to include a gas inlet or gas outlet in the conduits whichconnect the containers or in the functional medical device. Includedwithin the scope of the invention is the use of more than one gas inletor gas outlet in any one conduit, in any one blood product receivingcontainer, or in a functional biomedical device.

It will be apparent to one skilled in the art that the placement of agas inlet or a gas outlet may be optimized to achieve a desired result.For example, it may be desirable to locate the gas inlet upstream of thefunctional medical device and in or as close to the first container asis practical in order to maximize the recovery of blood product. Also,it may be desirable to locate the gas outlet downstream of thefunctional biomedical device and as close to the blood product receivingcontainer as is possible in order to maximize the volume of gas that isremoved from the system.

Such placement of the gas inlet or gas outlet is particularly desirablewhere there is only one gas inlet or gas outlet in the system. In someembodiments wherein the system includes more than one gas inlet and/orgas outlet, it may be desirable for the functional biomedical device toinclude the additional gas inlet and/or outlet. For example, as shown inFIG. 11, blood processing system 10 may include: a gas inlet 13 inconduit 12; and a functional biomedical device 14 including a gas inlet13A.

The gas inlet and the gas outlet is a porous medium designed to allowgas to pass therethrough. For the sake of convenience and clarity, theporous medium in the gas inlet or gas outlet shall be referred tohereinafter as a membrane.

As used herein, connector refers to any structure used to form a jointor to join itself to another piece. These connectors establish a flowpath through various elements of an assembly or system. Connector, asused herein, refers to penetrating connectors, such as a spike, cannula,or needle; and mating connectors, such as Luer-type, screw-type,friction-type, or connectors which are bonded together.

In accordance with the invention, blood product recovery from thevarious elements of the blood processing system may be maximized. Aftercentrifugation of the blood, the separate fractions of blood componentsare expressed to their respective receiving contains through theappropriate conduits and functional biomedical devices, if any. Bloodproduct that has become entrapped in these elements during processingmay be recovered either by passing purge gas through the conduits andbiomedical devices or by drawing at least a partial vacuum on the systemso as to draw out the entrapped liquid and to permit it to drain intothe appropriate receiving container. The purge gas may be provided fromany of a number of sources. For example, the blood processing system maybe provided with a storage container for the storage of the purge gas,the purge gas may be the gas that is removed from the system during theblood processing function, or the purge may be injected aseptically intothe system from an outside source (e.g., through a syringe). Forexample, it may be desirable to use sterile purge gas that has beensterilized in a separate container apart from the blood processingsystem.

The gas inlet of the present invention preferably includes a microporousmembrane in a housing. The gas inlet may comprise a microporous membranehaving both liquophobic and liquophilic layers, as described below, ormay comprise other structures which allow gas to enter the system, butdo not allow contaminants to enter. In a preferred embodiment, themicroporous membrane is preferably liquophobic, that is, it isnon-wettable. The membrane may also be liquophilic, but means should beincluded to keep the liquophilic membrane dry until ready for use. Forexample, while the blood product is being processed through the system,a clamp or other closure mechanism (such as a cap or sufficient pressuredifferential) may be used to avoid wetting the liquophilic membrane. Byliquophilic is meant that the microporous membrane layer is wetted bythe liquid being processed. The liquophilic membrane is capable ofpassing gas therethrough so long as it remains unsaturated by the liquidbeing processed.

The term liquophobic as used herein is effectively the obverse of theterm liquophilic; that is, a porous liquophobic material has a criticalwetting surface tension lower than the surface tension of the appliedliquid and is not readily or spontaneously wetted by the applied liquid.Liquophobic materials may be characterized, then, by a high contactangle between a drop of liquid placed on the surface, and the surface.Such high contact angle indicates poor wetting.

In accordance with the invention, gas may be removed from the bloodprocessing assembly or from in contact with a blood or blood product bypassing the air or gas through a gas outlet. The gas outlet may comprisea liquophobic membrane as described above, or may comprise otherstructures which allow gas to pass, but do not allow contaminants toenter. In a preferred embodiment, the gas outlet includes a multi-layermicroporous membrane in a housing. The first layer of the microporousmembrane is liquid-wettable, i.e., liquophilic, as noted above. Theliquophilic membrane is capable of passing gas therethrough so long asit remains unsaturated by the liquid being processed. The secondmicroporous membrane layer is not wettable by the liquid being processedby the delivery system, that is, the second layer is liquophobic.

The liquophilic layer of the multi-layer microporous membrane ispreferably positioned in the housing to the inward side of the gasoutlet so that the liquophilic layer is in direction communication witha conduit in which the gas outlet is to be carried. In this way theliquophilic layer is the first layer to be contacted either by gas thatis to be passed from the liquid transfer or delivery system or by theliquid being transferred or delivered by the system.

The liquophobic layer is also capable of passing gas therethrough. Theliquophobic layer may be superimposed on the liquophilic layer,preferably positioned on the outward side of the gas outlet. Theliquophobic layer is thus not contacted by either gas or liquid in thedelivery system until the gas or liquid has passed through theliquophilic layer. Because of the liquid-wettable character ofliquophilic layer and the non-wettable character of liquophobic layer,gas that contacts the gas outlet passes through the gas outlet so longas the liquophilic layer remains unwetted by liquid. Once theliquophilic layer becomes wetted with liquid, gas is no longer able topass through the liquophilic layer so the gas outlet becomes sealed orinactivated. Accordingly, after the liquophilic layer is wetted by theliquid being processed, gas from outside the delivery system isforeclosed from entering the system through the gas outlet. The combinedliquophobic and liquophilic membrane is particularly advantageous whenthe gas outlet is used in a closed sterile system; once any gasespresent in the system are vented, unwanted gases cannot reenter theclosed system through the gas outlet.

It will be appreciated that the liquophilic and liquophobic layers maybe two separate layers, or they may be bonded together. In addition, theinvention contemplates the use of a plurality of separate membraneelements combined together to form the liquophilic microporous membraneand the use of a plurality of separate membrane elements combinedtogether to form the liquophobic microporous membrane. By the termplurality is meant two or more. The plurality of separate membranelayers may be individually prepared and bonded together by various meansknown to those skilled in the art. For example, the separate membranelayers may be bonded together by drying two or more layers maintained inclose contact. Alternatively, by way of illustration and not inlimitation, the separate membrane layers may be prepared by passing thematerial used to form the membrane over a hot drum, against which themembrane is firmly held by a tensioned felt web or other process sheet.In addition, it is likewise possible to combine a suitable supportingsubstrate with the membrane layer, if desired, and the supportingsubstrate may serve as a permanent support.

In accordance with the invention the liquophobic microporous membranemust have sufficient liquophobicity with respect to the liquid to beprocessed in the liquid delivery or transfer system such that it willprevent the intrusion of the liquid being processed into the membrane.On the other hand the liquophilic microporous membrane must have a poresize and sufficient liquophilicity with respect to the liquid to beprocessed such that it will be wetted by the liquid sufficiently toprevent the passage of gas after it is wetted. It is preferred that boththe liquophilic and liquophobic microporous membranes have, whencombined for use in the gas outlet, an overall pore size such that themembranes form a bacterial barrier. When the pore size of themicroporous membranes is so chosen, the intrusion of bacteria into thesystem through the gas outlet is prevented. It will be readilyappreciated that a gas outlet so configured is particularly well adaptedfor a closed system and/or for sterile liquid processing systems.Preferably, particularly in medical applications, the system isgamma-sterilizable. Such gas outlet can even be used without a cap, ifdesired, although it is within the purview of the invention to cap thegas outlet if desired.

The microporous membrane may be made from a variety of materials. Thegas inlet and the gas outlet are porous media designed to allow gas topass therethrough. A variety of materials may be used to form the porousmedia provided the requisite properties of the particular porous mediumare achieved. These include the necessary strength to handle thedifferential pressures encountered in use and the ability to provide thedesired filtration capability while providing the desired permeabilitywithout the application of excessive pressure. In a sterile system, theporous medium should also preferably have a pore rating of 0.2micrometer or less to preclude bacteria passage. The porous medium maybe, for example, a porous fibrous medium, such as a depth filter, or aporous membrane or sheet. Multilayered porous media may be used, forexample, a multilayered porous membrane with one layer being liquophobicand the other liquophilic.

Preferred starting materials are synthetic polymers includingpolyamides, polyesters, polyolefins, particularly polypropylene andpolymethylpentene, perfluorinated polyolefins, such aspolytetrafluoroethylene, polysulfones, polyvinylidene difluoride,polyacrylonitrile and the like, and compatible mixtures of polymers. Themost preferred polymer is polyvinylidene difluoride. Within the class ofpolyamides, the preferred polymers include polyhexamethylene adipmide,poly-ε-caprolactam, polymethylene sebacamide, poly-7-aminoheptanoamide,polytetramethylene adipamide (nylon 46), or polyhexamethyleneazeleamide, with polyhexamethylene adipamide (nylon 66) being mostpreferred. Particularly preferred are skinless, substantiallyalcohol-insoluble, hydrophilic polyamide membranes, such as thosedescribed in U.S. Pat. No. 4,340,479.

Other starting materials may also be used to form the porous media ofthis invention including cellulosic derivatives, such as celluloseacetate, cellulose propionate, cellulose acetate-propionate, celluloseacetate-butyrate, and cellulose butyrate. Non-resinous materials, suchas glass fibers, may also be used.

It will be appreciated that if the material chosen is normallyliquophobic, and it is desired to use this material for the liquophobicmicroprous membrane, then the normally liquophobic material will have tobe treated so as to make it liquophilic. The nature of the material usedto make the membranes, the compatibility of the materials chosen for themembranes with one another and with the liquid to be processed all arefactors to be considered in selecting a particular material for amembrane for a given end application. However, quite apart from thoseconsiderations, it is generally desirable and preferable that the samematerial be used for both the liquophilic microporous membrane and forthe liquophobic microporous membrane so as to facilitate the bonding ofthe two different membranes to one another, if desired, as is preferred.

As noted above, the preferred material for both the liquophilicmicroporous membrane and the liquophobic microporous membrane ispolyvinylidene difluoride. Since polyvinylidene difluoride isliquophobic, it must be treated in order to render it liquophilic.Various treatments of the normally liquophobic polyvinylidene difluorideto render it liquophilic are known. However, the preferred method formaking the polyvinylidene difluoride material liquophilic is to treat aliquophobic polyvinylidene difluoride microporous membrane by subjectingit to gamma radiation in the presence of a liquophilic agent, such as,for example, hydroxyethylmethacrylate (HEMA). Preferably liquophilic andliquophobic polyvinylidene microporous membranes are secured to eachother by placing them in intimate contact and drying them on a drumdryer.

The rate of air flow through the microporous membrane of a gas outlet ora gas inlet can be tailored to the specific liquid transfer or deliverysystem of interest. The rate of air flow varies directly with the areaof the membrane and the applied pressure. Generally, the area of themembrane is designed to enable the liquid transfer or delivery system tobe primed in a required time under the conditions of use. For example,in medical applications it is desirable to be able to prime andintravenous set in from about 30 to about 60 seconds. In suchapplications as well as in other medical applications, the typicalmembrane may be in the form of a disc which has a diameter from about 1mm to about 100 mm, preferably from about 2 mm to about 80 mm, and morepreferably from about 3 mm to about 25 mm.

The pore size of the liquophilic and liquophobic microporous membranesis dependent on the liquid transfer or delivery system in which it isused, and, more particularly, whether the system is for medical ornon-medical use. By way of illustration, where the gas inlet or gasoutlet is to be incorporated in a system to be used for a medicalapplication, the pore size of the liquophilic and liquophobic membranesis preferably selected so that at least one of the membranes provides abacterial barrier to preclude entry of bacteria into the system. Thepore size of the liquophilic and liquophobic microporous membranes maybe the same or different. Generally the pore size of the liquophobicmembrane is in the range of from about 0.02 to about 3 micrometers andthe pore size of the liquophilic membrane is from about 0.04 to about 3micrometers. Preferably the pore size of the membranes is below about0.2 micrometers in order to maintain a suitable barrier to contaminantsand bacteria.

It will be appreciated that the pressure required to transfer gas in orout of the processing system through the gas inlet or gas outlet of thepresent invention varies inversely with the pore size of the membrane.Accordingly, the choice of pore size may be determined by theapplication in which the gas inlet or gas outlet is used. For example,since the pressure required to pass gas through the gas outlet increasesas the pore size of the membrane decreases, it may be desirable tochoose a larger pore size (consistent with the other objectives of, forexample, providing a bacterial barrier) where the delivery system is tobe operated by hand so that the pressure required to use the system doesnot become too great for convenient hand use.

The housing may be constructed of rigid plastic material that is alsotransparent, such as polyethylene, an acrylic such as polymethylmethacrylate, polymethyl acrylate, polymethyl pentene-1, polyvinylchloride, and vinyl chloride-vinylidene chloride copolymers. Translucentmaterials, such as polypropylene, polyethylene, urea-formaldehyde andmelamine-formaldehyde polymers, can also be employed. Other plasticmaterials that are particularly suitable are polystyrene, polyamides,polytetrafluoroethylene, polyfluorotrichloroethylene, polycarbonates,polyester, phenol-formaldehyde resins, polyvinyl butyral, celluloseacetate, cellulose acetate propionate, ethyl cellulose andpolyoxymethylene resins. Polyacrylonitrile polybutadiene-styrene (ABS)is preferred. It is intended that the invention should not be limited bythe type of housing being employed; other materials may be used, as wellas mixtures, blends, and/or copolymers of any of the above.

A metal housing can be used. Suitable metals include stainless alloys,such as nickel, chromium, vanadium, molybdenum, and manganese alloys.The housing material should, of course, be inert to the liquids beingprocessed.

The invention will be better understood by reference to the Figures. Inthese figures, like reference numerals refer to like parts.

FIGS. 1 through 5 and 11 show exemplary typical blood processing systemsin accordance with the invention, generally denoted as 10. The bloodprocessing set 10 includes a first container or blood collection bag 11,conduits 12 and 15, preferably flexible tubing, connecting the bloodcollection bag 11 and a second container (first satellite bag) 17 forreceiving a blood product, such as PRP. A functional biomedical device14 may be interposed between the collection bag 11 and the firstsatellite bag 17. As shown in FIGS. 2 and 4, collection bag 11 may alsobe connected via conduits 22 and 25, preferably flexible tubing, to athird container (second satellite bag) 27 for receiving a blood product,such as PRC; a functional biomedical device 24 may be interposed betweenthe collection bag 11 and the second satellite bag 27. In anotherembodiment of the invention, the blood processing assembly 10 may alsoinclude an additional (third) satellite bag 18 for receiving a bloodproduct, such as PC, which is connected to the first satellite bag 17via a conduit, preferably flexible tubing. At least one seal, valve, ortransfer leg closure or cannula (not illustrated) may also be positionedin the flexible tubing 12, 15, 22, and 25; this seal (or seals) isbroken or opened when fluid is to be transferred between bags.

The blood processing assembly 10, with one or more satellite bagsattached or connected via a conduit, may be used integrally or seriallyto separate components from whole blood.

It will be understood by those skilled in the art that the number andlocation of the gas inlet and gas outlet will depend upon the designcriteria for the blood processing system. For example, more than onesuch gas inlet or gas outlet may be included in any or all of theconduits 12, 15, 22, and 25; one or more gas inlets and gas outlets maybe included in the biomedical devices 14 and 24; and one or more gasinlets and gas outlets may be included in a blood or blood productcontainer, or in a port or ports in such containers. For example, asshown in FIG. 11, blood processing system 10 may include: a gas inlet 13in conduit 12; and a functional biomedical device 14 including a gasinlet 13A. In an embodiment of the invention in which a gas inlet 13 ispositioned in conduit 12 and a gas outlet 16 is positioned in conduit15, the gas inlet 13 is preferably placed as close to or in the firstcontainer as is practical in order to maximize the amount of bloodproduct recovered in the conduit and the biomedical device; and the gasoutlet 16 is preferably placed as close to the second container aspractical in order to maximize the amount of air and gases purged fromthe system. It is intended that the invention is not to be limited bythe number or placement of the gas inlet or gas outlet.

An embodiment of the invention includes a biological fluidadministration assembly (illustrated in FIGS. 9a and 9b) having afunctional biomedical device 14 defining a fluid flow path from anupstream end to a downstream end and having a connector 91 on theupstream end an a conduit 15 on the downstream end. Disposed in theconduit 15 is a branching element 60 in fluid communication with thedownstream end of the functional biomedical device, and having aconnector 93 on a downstream portion thereof. A gas inlet 13 or a gasoutlet 16, in accordance with the invention, is disposed in fluidcommunication with the branching element 60. A clamp 94 is preferablyincluded, and is used to regulate the flow of biological fluid or gasthrough the conduit. For example, if the functional biomedical device isa pre-primed filter, it may be desirable to close the clamp wheninserting the administration assembly into a fluid processing assemblyto avoid fluid loss during the connection procedure.

As has been noted above, it may be desirable to position a gas outlet asclose to the downstream connector as possible in order to remove as muchgas as is possible. Most desirable is removing all of the gas in thesystem. FIG. 9b illustrates an embodiment of the invention in whichsubstantially all of the gas in the system is removed, and in which thegas outlet 16 is part of the connector 96. The connector has a bodywhich defines a cavity, and a porous membrane for purging gastherethrough is positioned in the cavity. A sleeve on a downstreamportion of the body may be included in the body for positioning apenetrating connector 95, such as a spike. Once the gas outlet isclosed, clamped, or inactivated, the penetrating connector 95 may beused to pierce the porous membrane disposed in the body, therebyestablishing a flow path through the connector 96 and into a downstreamassembly or conduit.

The gas inlet and gas outlet may be included in the system in any of avariety of ways depending on the choice of the designer. By way ofexample, when the gas inlet 13 and/or gas outlet 16 is to be included ina conduit, the gas inlet and gas outlet may be incorporated intobranching element 60, such as a T-type connector (FIG. 9A) or a Y-typeconnector (FIG. 6C). As illustrated, the first leg 61 of branchingelement 60 accommodates a conduit through which blood enters thebranching element 60. A second leg 62 of branching element 60accommodates a downstream conduit. A gas inlet or gas outlet membrane isdisposed in the third leg 63 of the branching element 60. The membranemay be liquophobic, liquophilic, or a multilayered combination ofliquophobic and liquophilic layers. FIG. 6a shows a liquophilic layer 64and a liquophobic layer 65.

Each of the remaining components of the assembly will now be describedin more detail below:

The containers which are used in the blood processing assembly may beconstructed of any material compatible with whole blood or bloodproducts, and are capable of withstanding a centrifugation andsterilization environment. A wide variety of these containers arealready known in the art. For example, blood collection and satellitebags are typically made from plasticized polyvinyl chloride, e.g., PVCplasticized with dioctylphthalate, diethylhexylphthalate, ortrioctyltrimellitate. The bags may also be formed from a polyolefin,polyurethane, polyester, or polycarbonate.

As used herein, the tubing may be any conduit or means which providesfluid communication between the containers, and is typically made fromthe same flexible material as is used for the containers, preferablyplasticized PVC. A seal, valve, or transfer leg closure is typicallylocated within the tubing. A clamp or external closure device may alsobe used to regulate the flow of gas or blood product through a conduit.It is intended that the present invention is not limited by the type ofmaterial used to construct the containers or the conduit which connectsthe containers.

As noted above, a functional biomedical device may be any of a number ofdevices. Various filters, separators, debubblers, and connectors arealready known to practitioners in the art. In a preferred embodiment ofthe invention, the functional biomedical device includes one or more ofthe following: a platelet concentrator, a non-centrifugal plateletseparatory device, and one or more leucocyte-depletion devices.Exemplary devices for use with red blood cells are disclosed in U.S.Pat. Nos. 4,925,572 and 4,923,620, the descriptions of which are hereinincorporated by reference; an exemplary device for used with plateletsis disclosed in U.S. Pat. No. 4,880,548, the description of which isherein incorporated by reference. The fibers used in the PRC devicepreferably have a critical wetting surface tension (CWST) above about 53dynes/cm; for the platelet device, above about 70 dynes/cm. The fibersmay be natural fibers or may be treated or modified in order to achieveor increase the CWST. Also, the fibers may be bonded, fused, orotherwise fixed to one another, or they may be mechanically entwined.Other porous media, for example, open cell foamed plastics, surfacemodified as noted above, may be similarly used.

FIG. 1 illustrates an embodiment of the closed, sterile blood processingsystem of the present invention wherein gas inlet and gas outlet areincluded in the conduits in sealed communication with the satellitebags. The blood processing assembly 10 includes a first container 11 forcollecting or holding whole blood or a blood product and secondcontainer 17 for receiving a processed blood product, and conduits 12and 15 interconnecting the first container and the second container.Interposed between the containers is a functional biomedical device 14.The illustrated embodiment includes a gas inlet 13 in conduit 12upstream of biomedical device 14, and a gas outlet 16 in conduit 15downstream of the biomedical device 14. In this embodiment, air may beadded to the system through gas inlet 13 in order to recover blood or ablood product in conduit 12, biomedical device 14, and conduit 15. Inthis embodiment, gas in conduits 12 and 15 and biomedical device 14 isseparated from the blood product through gas outlet 16 and the separatedgas is vented from the system. The gas inlet 13 is preferably carried inconduit 12 as close as practical to first container 11 in order tomaximize the recovery of blood product. The gas outlet is preferablycarried in conduit 15 as close as is reasonably possible to satellitebag 17 to maximize the volume of gas vented from the system, andconcomitantly to minimize the volume of gas transferred into thesatellite bag. In another embodiment of the invention, illustrated inFIG. 3A, sterile air or gas may be retained in air container 32 untilready for use, at which point the gas is transferred into the system 10through conduit 31 and gas inlet 13. As illustrated, the bloodprocessing system 10 may also include a second air container 34 forholding air displaced from the system 10 through gas outlet 16 andconduit 33. An embodiment of the invention, illustrated in FIG. 3B,includes a single gas container 35, which serves as both a source andrepository of gas or air. Gas may enter conduit 12 through gas inlet 13by passing through conduit 37. Gas may be purged from the assemblythrough gas outlet 16 through conduit 36.

In another embodiment of the invention, e.g., as illustrated in FIG. 11,a blood processing system 10 includes a functional biomedical device 14interposed between first container 11 and second container 17. Thisillustrated embodiment includes a first gas inlet 13 upstream offunctional biomedical device 14, and the functional biomedical deviceincludes an additional gas inlet 13A. The gas inlets 13 and 13A allowair to pass therethrough, and preferably prevent bacteria from enteringthe system.

In another embodiment of the invention, illustrated in FIG. 2, the bloodprocessing system comprises multiple bags and multiple transfer lines.The fluid pathway that leads from first container 11 to second container17 is exemplary of a typical PRP processing configuration. The fluidpathway that leads from first container 11 to third container 27 isexemplary of a typical PRC processing configuration. Similar to thepreviously described fluid pathways, the illustrated pathway includesfirst container 11 for collecting or holding whole blood or a bloodproduct and third container 27 (for receiving a processed bloodproduct), and a conduit 22 and 25 interconnecting the first containerand the third container. Interposed between the containers is afunctional biomedical device 24. The illustrated embodiment includes agas inlet 23 in conduit 22 upstream of biomedical device 24, and a gasoutlet 26 in conduit 25 downstream of the biomedical device 24. FIG. 4is similar to FIG. 3 in the inclusion of first air container 43 foradding air/gas to the system 10 and second air container 46 for holdingair transferred out of the system 10. As illustrated, first aircontainer 43 may supply air/gas to the system through conduit 41 and gasinlet 23, as well as through conduit 42 and gas inlet 13. Asillustrated, gas may be removed from the system 10 into second aircontainer 46 through gas outlet 26 and conduit 44, as well as throughgas outlet 16 and conduit 45. Fourth container 18 is included toillustrate that other containers may be included in the blood processingsystem 10.

In an embodiment of the invention, a gas inlet or a gas outlet arecapable of being penetrated, aseptically as for example, by a syringe orthe like, to permit sterile gas to be injected into the system throughthe membrane to facilitate the recovery of entrapped blood components inthe system, or to draw gas or air from the system. For example, FIG. 9bshows a gas outlet 16 as part of connector 96. Connector 96 ispositioned in the downstream and of conduit 15, and includes gas outlet16 and a sleeve for accommodating a penetrating connector 95.

In another embodiment of the invention, the assembly does not includeany containers, but does include the elongate for establishing a flowpath which utilizes a gas inlet and/or a gas outlet. An example of theseassemblies is illustrated in FIG. 5. The assembly 10 includes apenetrating connector 50 on one end and a receiving connector 51 on theother. Interposed between the connectors 50 and 51 are a conduit 12, gasinlet 13, functional biomedical device 14, conduit 15, and gas outlet16. Gas inlet 13 is preferably positioned in conduit 12 as close toconnector 50 as practical, and gas outlet 16 as close to connector 51 aspractical.

In another embodiment of the invention, illustrated in FIG. 10, a gasinlet 16 is cooperatively arranged with a collection receptacle 11. Aclamp, closure, or other means may be used for opening and closingaccess to the receptacle. As illustrated, the gas inlet 16 is part of aconnector 96 should it be desirable to establish communication betweenthe gas inlet and a gas source. When making the connection to anotherelement, such as an air container, it is preferable that the membrane inthe gas inlet is not pierced by the mating connector.

It will be appreciated that the invention may be modified to includerecovery and recycle of the gas in the system, or it may be modified toinclude a separate gas purge reservoir as discussed above (see FIGS. 3and 4),

One skilled in the art will recognize that the invention as describedhere may be reconfigured into different combinations. These differentconfigurations and combinations are included within the scope of theinvention.

In general, the donor's blood is received directly into the bloodcollection bag 11, which may be connected to a satellite bag 17 for PRPand/or a satellite bag 27 for PRC. Preferably, the PRP satellite bag isin turn connected to a satellite bag 18 for PC.

Movement of blood or a blood product through the system is effected bymaintaining a pressure differential between the collection bag and thedestination of the blood or the blood product (e.g., a satellite bag ora needle on the end of a conduit). Exemplary means of establishing thispressure differential may be by gravity head, applying pressure to thecollection bag (e.g., by hand or with a pressure cuff), or by placingthe satellite bag in a chamber which establishes a pressure differentialbetween the satellite bag and the collection bag (e.g., a vacuumchamber).

Once the pressure differential is established and any clamps are opened,a column of blood or blood product is driven through conduit 12 or 22,through functional biomedical device 14 or 24, into conduit 15 or 25,and into the first leg 61 of branching element 60. A clamp is placedbetween satellite bag 17 or 27 and gas outlet 16 or 26. As the blood orblood product advances, it pushes gas in the conduit ahead of it untilthe gas reaches branching element 60. At branching element 60, gas aheadof the liquid column moves into the third leg 63 of branching element 60and is vented from the system through gas outlet 16 or 26. As the liquidin conduit 15a or 25a continues its travel through the second leg 62 ofbranching element 60 and into conduit 15 or 25 leading from branchingelement 60 to receiving container 17 or 27, gas in conduit 15 or 25 isdisplaced toward and into the third leg 63 of branching element 60 whereit passes out of the blood processing system through first layer 64second layer 65 of gas outlet 16 or 26. As gas in conduit 15a or 25a isdisplaced by advancing liquid, the liquid being transferred fillsconduit 15b or 25b with liquid. After conduit 15b or 25b is filled withliquid, third leg 63 of branching element 60 also fills with liquid. Theliquid then contacts and wets the first layer 64 of gas outlet 16 or 26.Wetting of first layer 64 by the liquid seals or inactivates gas outlet16 or 26 to the passage of gas and thus forecloses air from outside thesystem from entering into the system through gas outlet 16 or 26.

A clamp is normally closed in order to allow gas in the conduit 15a,functional biomedical device 14, and gas outlet 16 to be purged from thesystem 10, and to prevent gas in the system from entering satellite bag17. After the entire conduit line has been primed, the clamp is openedto allow blood product to flow into satellite bag 17.

In operation, as a column of blood and/or blood product flows from thefirst container 11 through the conduit means 12 or 22 and the biomedicaldevice 14 or 24 toward the satellite bag 17 or 27, it pushes gas inthose elements toward branching element 60. At branching element 60, gasahead of the column of blood and/or blood component moves into the thirdleg 63 of branching element 60. Since the gas gasses through theliquophobic porous medium, but the blood and/or blood products do not,the gas is separated from the blood products and is precluded fromentering the satellite bag. The gas outlet may comprise a liquophobicporous medium having a pore size of not greater than 0.2 microns and maybe included in one leg of a branching connector.

The gases separated by the gas outlet 16 or 26 may be vented from thesystem, or they may be collected in gas container 35 (as noted below)and returned to the system as a purge gas to facilitate the recovery ofblood and blood product that becomes trapped in the various componentsof the system.

After the system is primed and the gas outlet is inactivated, the clampadjacent to the satellite bag 17 or 27 is opened to allow the satellitebag to fill with processed blood product. This continuous untilcontainer 11 collapses. In order to recover the very valuable bloodproduct retained in the system, ambient air or a sterile gas may enterthe system through gas inlet 13 or 23. If gas inlet 13 or 23 is a manualinlet means, a closure is opened or a clamp released; if the gas inlet13 or 23 is automatic, the pressure differential between the gas inletand satellite bag 17 or 27 will cause the air or gas to flow throughconduit 12 or 22, through biomedical device 14 or 24, and towardsatellite bag 17 or 27. In the process, retained blood or blood productthat is trapped in those elements during processing are recovered fromthose components and collected in satellite bag 17 or 27. It should benoted that the purge air or gas is preferably separated from the bloodproduct at gas outlet 16 or 26, so that little, if any, purge gas willbe received by satellite bag 17 or 27. This may be accomplished byclamping the conduit 15b or 25b downstream of the gas outlet 16 or 26.In another embodiment of the invention, the purge air or gas may beseparated from the system through a gas outlet located in the bagitself. Under typical conditions, the blood or blood product will drainthrough the system until flow is stopped. In a typical device, the flowmay stop when about half of the functional biomedical device is emptied.

It will be appreciated that when the blood or blood product from thedonor bag 11 is expressed to the satellite bags 17 and 27, some of theblood or blood product may be trapped in conduits 12, 55, 22, and 25 andin biomedical devices 14 and 24. For example, 8 cc to 35 cc is typicallyretained in the system; but as little as 2 cc to as much as 150 cc ormore may be retained in some types of systems. In an embodiment of theinvention air or gas may be stored in gas container 32, 35, or 43; uponopening of valve or clamp means in conduits 31, 37, 41, or 42, gas canbe fed through conduits 31, 37, 41 or 42 to purge conduits 12 and 22,and biomedical devices 14 and 24, thereby facilitating the recovery ofblood components that may have been trapped in the conduits andbiomedical devices during processing.

Preferably, the purge air or gas is fed to conduits 12 and 22 at a pointas close as is reasonably possible to blood receiving bag 11 to maximizethe volume of blood component recovered. Air or gas container 32, 35, or43 is preferably flexible so that the gas therein may be fed to thesystem merely by simple compression. Container 11, air or gas container32, 35, or 43, and satellite bags 17, 18, or 27 may be composed of thesame material.

In another embodiment of the invention, a purge gas reservoir 35 isprovided. Purge gas reservoir 35 is in sealed communication with bloodreceiving bag 11 through valve or clamp means in conduits 36 and 37.Purge gas reservoir 35 is preferably flexible so that gas therein may befed to the system merely by simple compression, and the bag may be madeof the same materials as are container 11 and satellite bags 17, 27.

After the blood in receiving bag 11 is processed, valve or clamp meansin conduit 33, 36, 44 or 45 is opened, and purge gas reservoir 34, 35,or 46 receive transferred gas.

It will be appreciated that gas outlet 16 and 26 can also be used toprime a liquid transfer or delivery system which is used for thepercutaneous injection of liquids into a patient. Such systems,including, example, an intravenous injection system as illustrated inFIG. 7, comprise a collapsible container 11 which contains the liquid tobe transferred or delivered, a drip chamber 81 for indicating ormonitoring the flow of liquid injected into the patient, and a conduit82 in communication with the container 11 and drip chamber 81 andleading from drip chamber 81 to the injection needle or the like (notshown). In accordance with this embodiment of the present invention, gasoutlet 16 as described above is carried in conduit 82 downstream of dripchamber 81 but upstream of the terminal end of conduit 82.

To prime the system, container 11 is collapsed sufficiently to drive acolumn of liquid into the drip chamber 81 which has an air space 83therein, which has been created, for example, by briefly inverting thedrip chamber 81. The moving column of liquid from drip chamber 81 drivesa head of gas in the portion of conduit 82 extending from drip chamber81 toward the terminal end of conduit 82. When the head of gas reachesgas outlet 16, it is passed out of conduit 82 in the same manner asdescribed above.

It will be understood that while the invention has been described inconnection with the preferred embodiment, alternative embodiments arealso possible. For example, it is possible for blood collection bags toreceive blood components from one of the satellite bags, if desirable,and it is likewise within the contemplation of the invention to usesatellite bags that are partitioned internally and are capable ofreceiving different blood component in the same satellite bag.

What is claimed is:
 1. A biological fluid processing system comprising:afirst container; a second container downstream of the first container; afunctional biomedical device comprising a leukocyte depletion filter influid communication with and interposed between the first container andthe second container; a gas inlet for allowing gas to reach thefunctional biomedical device and to displace biological fluid from thebiomedical device, said gas inlet comprising at least one porous mediumincluding a membrane for passing gas therethrough, wherein the gas inletis disposed between the functional biomedical device and the firstcontainer.
 2. The system of claim 1 wherein the porous medium of the gasinlet comprises a membrane selected from the group consisting of aliquophobic membrane, a liquophilic membrane, and a layered membranehaving at least one liquophobic layer and at least one liquophiliclayer.
 3. The system of claim 2 comprising a closed, sterile system. 4.The system of claim 1 wherein the gas inlet allows gas to passtherethrough but blocks the passage of bacteria.
 5. The system of claim1 further comprising an additional gas inlet for allowing gas to reachthe functional biomedical device and to displace biological fluid fromthe biomedical device, said gas inlet comprising at least one porousmedium for passing gas therethrough wherein the functional biomedicaldevice includes the additional gas inlet.
 6. The system of claim 5comprising a closed, sterile system.
 7. The system of claim 1 whereinthe porous medium of the gas inlet comprises a liquophobic membrane. 8.The system of claim 1 wherein the first and second containers areflexible containers.
 9. The system of claim 1 wherein the porous mediumof the gas inlet comprises a membrane sheet.
 10. The system of claim 1wherein the first container includes the gas inlet in a wall of thecontainer.
 11. The system of claim 1 wherein the second containerincludes a gas outlet comprising a porous medium for passing gastherethrough.
 12. A biological fluid processing system comprising:afirst container; a second container downstream of the first container; afunctional biomedical device comprising a leukocyte depletion medium influid communication with and interposed between the first container andthe second container; a gas inlet for allowing gas to reach thefunctional biomedical device and to displace biological fluid from thebiomedical device, said gas inlet comprising at least one porous mediumfor passing gas therethrough, wherein the gas inlet is disposed betweenthe first container and the functional biomedical device; and at leastone gas outlet comprising at least one porous medium for passing gastherethrough, wherein the gas outlet is disposed between the leukocytedepletion medium and the second container.
 13. The system of claim 12wherein at least one porous medium in each of the gas inlet and the gasoutlet comprises a membrane.
 14. The system of claim 12 wherein theporous medium of the gas outlet comprises a membrane selected from thegroup consisting of a liquophobic membrane, a liquophilic membrane, anda layered membrane having at least one liquophobic layer and at leastone liquophilic layer.
 15. The system of claim 12 wherein the system isa closed, sterile blood processing system.
 16. The system of claim 12further comprising at least one conduit interposed between thefunctional biomedical device and the second container, wherein the gasoutlet is carried in the conduit downstream of the functional biomedicaldevice.
 17. The system of claim 16 comprising a closed, sterile system.18. The system of claim 12 wherein the gas outlet allows gas to passtherethrough but blocks the passage of bacteria.
 19. The system of claim12 wherein the first and second containers are flexible containers. 20.The system of claim 12 wherein the porous medium of the gas outletcomprises a membrane sheet.
 21. A biological fluid processing assemblycomprising:a leukocyte depletion device for providing leukocyte depletedbiological fluid, said leukocyte depletion device comprising a housinghaving an inlet and an outlet and defining a fluid flow path between theinlet and the outlet, and a leukocyte depletion medium disposed in thehousing across the fluid flow path; a first conduit in fluidcommunication with the inlet of the leukocyte depletion device; and atleast one gas inlet upstream of the leukocyte depletion device, saidfirst gas inlet comprising a porous medium including a membrane forpassing gas therethrough, said first gas inlet in fluid communicationwith the leukocyte depletion device and the first conduit, wherein saidfirst gas inlet allows gas to pass therethrough to the leukocytedepletion device, and to displace biological fluid from the leukocytedepletion device.
 22. The assembly of claim 21 further comprising atleast one gas outlet comprising a porous medium for passing gastherethrough, said gas outlet in fluid communication with the leukocytedepletion device.
 23. The assembly of claim 22 wherein the gas inlet andthe gas outlet block the entry of bacterial into the assembly.
 24. Theassembly of claim 22 further comprising a container downstream of theleukocyte depletion device, said container being suitable for containingleukocyte depleted biological fluid.
 25. A method for processing abiological fluid in a closed sterile system comprising:passing thebiological fluid from a first container through a functional biomedicaldevice comprising a porous leukocyte depletion medium for leukocytedepleting the biological fluid, and collecting leukocyte depletedbiological fluid in a second container downstream of the functionalbiomedical device; opening a gas inlet comprising a porous mediumsuitable for passing gas therethrough and allowing gas to pass throughthe porous medium of the gas inlet, and passing said gas to thefunctional biomedical device; and, while maintaining the closed sterilesystem, collecting additional leukocyte depleted biological fluid intothe second container, said biological fluid being displaced by the gas.26. The method of claim 25 further comprising closing the gas inlet. 27.The method of claim 25 wherein the biological fluid is blood or a bloodproduct.
 28. A method for processing a leukocyte containing biologicalfluid comprising:passing the leukocyte containing biological fluidthrough a leukocyte depletion filter assembly including a poroussynthetic polymeric leukocyte depletion medium to deplete leukocytesfrom the biological fluid; passing gas to the filter assembly through agas inlet upstream of the filter assembly, said gas inlet comprising aporous medium, wherein the gas displaces biological fluid from thefilter assembly; and collecting the leukocyte depleted biological fluidpassing through the filter assembly.
 29. The method of claim 28 whereinthe biological fluid comprises blood or a blood product.
 30. The methodof claim 28 comprising processing biological fluid in a sterile closedsystem.
 31. The method of claim 28 including passing leukocyte depletedfluid into a container downstream of the leukocyte depletion filterassembly.
 32. The method of claim 28 wherein the leukocyte containingbiological fluid is passed from a container upstream of the filterassembly, wherein the container includes the gas inlet.
 33. The methodof claim 28 wherein the gas inlet comprises a microporous membrane. 34.The method of claim 33 wherein the gas inlet comprises a liquophobicmembrane.
 35. A method for processing a leukocyte containing biologicalfluid comprising:passing the leukocyte containing fluid through aleukocyte depletion filter assembly including a porous syntheticpolymeric leukocyte depletion medium to deplete leukocytes from thebiological fluid, wherein passing biological fluid through the mediumdisplaces a gas; passing gas displaced by the biological fluid through agas outlet in fluid communication with the leukocyte depletion medium,said gas outlet comprising a porous medium; passing gas to the filterassembly through a gas inlet in fluid communication with the leukocytedepletion medium, said gas inlet comprising a porous medium, wherein thegas passed through the gas inlet displaces biological fluid from thefilter assembly; and collecting the leukocyte depleted biological fluidpassing through the filter assembly.
 36. A biological fluid processingsystem comprising:a leukocyte depletion device comprising a leukocytedepletion medium; a gas inlet for allowing gas to reach the leukocytedepletion device and to displace biological fluid from the leukocytedepletion device, said gas inlet comprising at least one porous mediumincluding a membrane for passing gas therethrough; a gas outlet forpassing gas displaced by biological fluid, said gas outlet comprising atleast one porous medium including a membrane for passing gastherethrough.
 37. The system of claim 36 wherein the leukocyte depletiondevice includes the gas inlet.
 38. The system of claim 36 wherein thegas inlet is upstream of the leukocyte depletion device.
 39. The systemof claim 36 wherein the leukocyte depletion device includes the gasoutlet.
 40. The system of claim 36 wherein the gas outlet is downstreamof the leukocyte depletion device.
 41. The system of claim 36 whereinthe gas outlet includes a membrane having a liquophilic layer.
 42. Thesystem of claim 36 wherein the gas outlet includes a membrane having aliquophobic layer.
 43. The system of claim 36 wherein the gas outletincludes a membrane having a liquophilic layer and a liquophobic layer.